Extracorporeal medical machines such as the pump-oxygenator and artificial kidney rely on systemic heparinization to improve blood compatibility. However, heparin can lead to serious complications such as bleeding. With the prospect of even longer perfusion times with machines such as the membrane oxygenator, the problems due to heparinization become more severe. Although many approaches have been explored to solve this problem, such as the use of neutralizing compounds or heparin bonded surfaces, there still remains no real alternative to systemic heparinization. We propose a new method to control heparin levels using a blood filter containing immobilized heparinase. Such a filter might be used in situations where it is desired to heparinize the extracorporeal circuit without simultaneous heparinization of the patient. Alternatively, it could eliminate the use of neutralizing compounds such as protamine. The objective of this proposal is to develop and evaluate such a selective means of removing heparin from blood. The specific aims are (1) isolation and purification of heparinase, (2) immobilization of the enzyme and design of the heparin removal system and (3) in vivo testing of the heparinase filter.